All inclusion and exclusion criteria apply to both phase I and II patients.

Inclusion Criteria:

- Subjects with histologically proven intracranial glioblastoma multiforme (GBM) and
gliosarcoma will be eligible for this protocol.

- Gadolinium MRI or contrast CT must be obtained within 14 days prior to registration.

- Patients must have a plan to begin treatment with ZD6474 (vandetanib) and/or
temozolomide 21 to 35 days after surgical resection or 14 to 35 days after
stereotactic biopsy.

- Subjects must have a plan to begin partial brain radiotherapy 5-7 days after
beginning ZD6474. Radiotherapy must be a) at the Radiation Oncology Department of
the participating institution, b) at an affiliated site that is currently approved to
participate in any trial of the Radiation Therapy Oncology Group (RTOG), or c) at
another location with prior approval from the Overall PI of the trial. Radiotherapy
must be given by external beam to a partial brain field in daily fractions of 180 to
200 cGy, to a planned total dose to the tumor of approximately 6000 cGy. Stereotactic
radiosurgery and brachytherapy will not be allowed.

- If it is deemed in the best interest of the patient, intensity modulated radiation
therapy (IMRT) is allowable on this trial. If IMRT is administered, dose specifics
must be conducted per institutional guidelines.

- Subjects must be willing to forego other cytotoxic and non-cytotoxic drug therapy
against the tumor while being treated with ZD6474 (ZactimaTM), with the exception of
temozolomide.

- All subjects must sign an informed consent indicating that they are aware of the
investigational nature of this study prior to any study-related procedures. Patients
must be registered with in the Dana Farber Cancer Institute's Quality Assurance
Office for Clinical Trials prior to treatment with ZD6474 (Vandetanib). Patients must
sign an authorization for the release of their protected health information.

- Subjects can be male or female, and must be >/= 18 years old, with a life expectancy
> 12 weeks.

- Subjects must be able to care for themselves (KPS>/=60).

- Subjects must have adequate labs as defined below:

- Patients must have adequate bone marrow function (WBC >/= 3,000/μl, ANC >/=
1,500/mm3, platelet count of >/= 100,000/mm3, and hemoglobin >/= 10 gm/dl),
adequate liver function (SGOT, SGPT ULN), and adequate renal function (creatinine < 1.5 mg/dL, and/or serum
creatinine 30 mL/min, calculated by
Cockcroft-Gault formula) before starting therapy. These tests must be performed
within 14 days prior to registration. Eligibility level for hemoglobin may be
reached by transfusion.

- Patients must have potassium >/= 4.0 mmol/L and serum calcium (ionized or
adjusted for albumin) or magnesium in the normal range (supplementation is
allowed).

- Patients' alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
must be
- Women of childbearing potential must have a negative pregnancy test documented within
14 days prior to registration.

- Men and women of childbearing potential must agree to use adequate contraception
while receiving study medication and continue for at least two months (five
half-lives) after their last dose of study medication.

- Patients must have sufficient tissue available from their prior biopsy/surgery: at
least 10 (preferably 20) unstained slides or 1 tissue block.

- Patients must agree not to donate blood during the trial and for 3 months following
their last dose of trial treatment

Exclusion Criteria:

- Subjects must not have had prior cranial radiation therapy.

- Subjects must not have received prior cytotoxic drug therapy, non-cytotoxic drug
therapy, or experimental drug therapy for brain tumors.

- Subjects must not have received prior Gliadel wafers.

- Subjects must not have received any investigational agents within 30 days prior to
commencing study treatment

- Subjects must not have evidence of severe or uncontrolled systemic disease or any
concurrent condition that in the investigator's opinion cannot be adequately
controlled with appropriate therapy or would compromise the patient's ability to
tolerate this therapy.

- Subjects with a history of any other cancer (except non-melanoma skin cancer or
carcinoma in-situ of the cervix), unless in complete remission and off of all therapy
for that disease for a minimum of 3 years are ineligible.

- Subjects must not have any unresolved toxicity greater than CTC grade 1 related to
previous anti-cancer therapy.

- Subjects must not have active infection.

- Subjects must not be pregnant/breast feeding.

- Subjects must not have any disease that will obscure toxicity or dangerously alter
drug metabolism.

- Subjects must not have history of any clinically significant cardiac event, or
evidence of heart disease.

- No event such as myocardial infarction or superior vena cava syndrome (SVC); New
York Heart Association (NYHA) classification of heart disease >/= 2 within 3
months before entry; or presence of cardiac disease that, in the opinion of the
Investigator, increases the risk of ventricular arrhythmia.

- No history of arrhythmia (multifocal premature ventricular contractions (PVCs),
bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial
fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or
asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled
on medication is not excluded.

- No previous history of QTc prolongation as a result from other medication that
required discontinuation of that medication.

- No congenital long QT syndrome, or1st degree relative with unexplained sudden
death under 40 years of age.

- No left bundle branch block (LBBB).

- Subject's screening ECG cannot indicate QTc (with Bazett's correction) that is
either unmeasurable or >/= 480 msec on. If subject's screening QTc >/= 480 msec,
it may be repeated twice (at least 24 hours apart). The average QTc from the 3
screening ECGs must be < 480 msec. Patients who are receiving a drug that has a
risk of inducing Torsades de Pointes are excluded if QTc is >/= 460 msec.

- Subjects must not be taking any enzyme-inducing anti-epileptic drugs (EIAED) or other
drugs that are potent inducers of CYP3A4 function (rifampicin, rifabutin, phenytoin,
carbamazepine, phenobarbitol and St. John's Wort). If patients were previously on
EIAEDs and these have been discontinued, patients must have been off the agent for at
least 7 days prior to registration.

- Subjects must not be taking concomitant medications known to prolong the QT interval
and have a risk of inducing Torsade de Pointes (TdP). Any concurrent medication with
a known risk of inducing TdP that, in the investigator's opinion cannot be
discontinued, will be allowed; however, these patients must be monitored closely.

- Subjects must not have uncontrolled hypertension (high blood pressure).

- Subjects must not have active diarrhea that may affect the ability of the patient to
absorb or tolerate ZD6474 (Vandetanib).

- Subjects with confirmed diagnosis of human immunodeficiency virus (HIV) infection are
excluded at the investigator's discretion if he/she feels that 1) a potential drug
interaction between ZD6474 (Vandetanib) and any of the patient's anti-HIV medications
could influence the efficacy of the anti-HIV medication, or 2) it may place the
patient at risk due to the pharmacologic activity of ZD6474 (Vandetanib).

- Subjects' pre-operative MRI must not demonstrate significant intratumoral or
peritumoral hemorrhage & post-operative MRI must not demonstrate a large amount of
peri-operative parenchymal hemorrhage. (Patients may have postoperative intracavitary
blood.)

- Subjects must not have had major surgery (unrelated to the glioblastoma) within 4
weeks before starting study therapy, and subjects cannot have a surgical incision
that has not completely healed before starting study therapy.

- Subjects must not be receiving Coumadin (subjects may take low molecular weight
heparin).

- Subjects must not have enrolled on this trial previously.

- Subjects must have had no involvement in the planning or conduct of the study
(applies to both AstraZeneca staff or staff at the study site).

- Any of the following lab results will result in patient exclusion from trial:

- Potassium: < 4.0 mmol/L despite supplementation, or above the CTCAE grade 1
upper limit.

- Magnesium below the normal range despite supplementation, or above the CTCAE
grade 1 upper limit.

- Serum calcium above the CTCAE grade 1 upper limit.

NOTE: In cases where the serum calcium is below the normal range, 2 options would be
available:

- The calcium adjusted for albumin is to be obtained and substituted for the measured
serum value. Exclusion is to then be based on the adjusted for albumin values falling
below the normal limit.

- Determine the ionized calcium levels. If these ionized calcium levels are out of
normal range despite supplementation, then the patient must be excluded.